Boron neutron capture therapy (hereinafter, also referred to as “BNCT”) for cancer is a radiation therapy that impairs tumor cells with alpha particles and 7Li particles that result through the capture reaction between 10B nucleus that has been taken up by the tumor tissues and a thermal neutron beam that generally does not affect the body. Since the pathway of the particle radiation resulting from this nuclear reaction is almost equal to the diameter of the cell, if boron can be accumulated only in the tumor tissues at a high concentration in advance, they can be irradiated with thermal neutron so that the tumor tissues can cell-selectively impaired with a minimum damage on normal tissues. Accordingly, therapeutic effects can be expected even in tumors that are less susceptible to radiation or in infiltrative tumors. Clinical studies have been conducted on recurrent cases of malignant brain tumor (glioblastoma) and head and neck cancer that are clinically infiltrative and that have adverse prognosis, and good results have been reported (Non-patent Document 1).
A clinically used boron compound is a monomolecular compound of boronophenylalanine (BPA) and a boron ion cluster called BSH. Although these compounds have been clinically applied, they are not adequate in terms of accumulation in the tumors and thus the attempt to further enhance the boron concentration ratio in tumor and normal tissues (T/N ratio) has been continued. In addition, techniques for entrapping a hydrophilic boron compound such as BHA (10B-enriched 4-Borono-L-phenylalanine, C9H1210BNO4) or BSH (10B-enriched Sodium mercaptododecaborate, BSH [CAS No. 12448-24-7], [10B12H11SH]Na2) into a liposome whose surface has been covered by polyethylene glycol (PEG) are used as a technique for accumulating a high concentration of boron only in the tumor tissues (Non-patent Document 2).
However, according to these methods, there have been major issues of radiation damage on the normal tissues caused by boron in the normal tissues and poor therapeutic effect due to incompatibility between difficulty in accumulating boron to an effective therapeutic range and accomplishment of targeted T/N ratio.
Another technique has also been developed in which a boron compound is entrapped in a phospholipid bilayer through covalent bonding between a lipid and an aqueous boron compound. However, this requires multiple and complicated steps for synthesis, and thus numbers of problems remain in terms of efficiency and cost. Moreover, several cases of acute toxicity have been reported in animal experiments, leaving problems also in terms of safety (Non-patent Document 3).